Résumé :
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Emery-Dreifuss Muscular Dystrophy (EDMD) is a rare autosomal or X-linked recessive condition, associating muscular dystrophy, joint contractures and cardiac disease. X-linked forms are caused by EMD gene mutations (Emerin). Since the identification of the causative gene in 1994, routine molecular diagnosis of emerinopathies in France has been exclusively performed in the laboratoire de biochimie et génétique moléculaire (LBGM) at Cochin hospital (Paris). We aimed to perform a retrospective assessment of the LBGM’s 14 years experience in this field. During the 1994-2008 period, 379 patients (239 families, 13 countries) have been referred to LBGM for emerin analysis. Where Emerin protein expression was not studied by immunofluorescence (IF), western blot (WB) was performed on muscle or lymphoblastoid cell lines when available. EMD gene was secondarily studied by sequencing method. An EMD mutation was identified in 139 subjects (83M / 56F) corresponding to 53 families. Previous Emerin analysis in 83 of them had showed an abnormal IF and/or Emerin expression (absent, reduced, mosaic) in 78 patients while it was normal for the remaining 5 (female carriers). EMD mutations were out-of frame insertions/deletions (23 families), in-frame deletions/insertions (5 families), point mutations (non sense in 17 families, missense in 1 family) and intronic mutations (7 families) Clinically, the 76 male subjects had EDMD while the others had isolated cardiac disease (5) or were still asymptomatic (2). 45 female carriers were asymptomatic while 11 (19%) showed clinical symptoms of disease (6 EDMD, 4 isolated cardiac disease and 1 limb girdle myopathy) due to variable degree of X chromosomes reciprocal inactivation. Finally, this retrospective analysis revealed a large cohort of mutated cases (53 families, 21% of the referred cohort) and that Emerin IF / WB analysis remain a good pre-screening tool before molecular analysis of the EMD gene.
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